Inhibition of testosterone metabolism in the brain and cloacal gland of the quail by specific inhibitors and antihormones

1987 ◽  
Vol 112 (2) ◽  
pp. 189-195 ◽  
Author(s):  
C. Alexandre ◽  
J. Balthazart
Keyword(s):  
Reductase Inhibitor ◽  
Aromatase Activity ◽  
Testosterone Metabolism ◽  
In Vivo Experiments ◽  
High Doses ◽  
The Brain ◽  
Very High ◽  
Cloacal Gland

ABSTRACT The effects of antioestrogens, antiandrogens and of various inhibitors of testosterone metabolism on testosterone metabolism in the quail hypothalamus and cloacal gland were studied by an in-vitro radio-enzymatic assay. It was found that antioestrogens and antiandrogens generally had little or no effect on aromatase and 5α- and 5β-reductases of testosterone, except when used at very high doses. The 5α-reductase inhibitor, 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one, inhibited both 5α- and 5β-dihydrotestosterone production without markedly affecting aromatase activity. Surprisingly, the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione, inhibited not only the production of oestradiol but also that of 5β-dihydrotestosterone and, to a lesser extent, 5α-dihydrotestosterone. These unexpected properties should be taken into account when interpreting the results of in-vivo experiments using these compounds. J. Endocr. (1987) 112, 189–195

Changes in testosterone metabolism by the brain and cloacal gland during sexual maturation in the Japanese quail (Coturnix coturnix japonica)

1984 ◽  
Vol 100 (1) ◽  
pp. 13-18 ◽  
Author(s):  
J. Balthazart ◽  
M. Schumacher
Keyword(s):  
Japanese Quail ◽  
Sexual Maturation ◽  
Reductase Activity ◽  
Coturnix Japonica ◽  
Testosterone Metabolism ◽  
Coturnix Coturnix ◽  
The Brain ◽  
Very High ◽  
Cloacal Gland

ABSTRACT Testosterone metabolism in the brain and pituitary and cloacal glands of male and female Japanese quail was studied in vitro during sexual maturation (from 1 day to 5 weeks after hatching). The production of 5α-dihydrotestosterone in the hyperstriatum and cloacal gland and that of androstenedione in the cloacal gland of males was highest at 1 day after hatching, which could be related to the peak of plasma androgens previously demonstrated in neonatal quail. 5β-Reductase activity was very high in the brain, but not the pituitary or cloacal glands of young chicks and decreased markedly, especially in the hypothalamus, during sexual maturation. As 5β-reduced metabolites of testosterone are inactive androgens, it is suggested that the decrease of 5β-reductase activity with age corresponds to a potentiation of the effects of testosterone at the level of the brain. J. Endocr. (1984) 100, 13–18

scholarly journals Boosting GSH Using the Co-Drug Approach: I-152, a Conjugate of N-acetyl-cysteine and β-mercaptoethylamine

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1291 ◽  
Author(s):  
Rita Crinelli ◽  
Carolina Zara ◽  
Michaël Smietana ◽  
Michele Retini ◽  
Mauro Magnani ◽  
...  
Keyword(s):  
Cell Cultures ◽  
In Vivo Studies ◽  
In Vivo Metabolism ◽  
Pharmacokinetic Properties ◽  
Immunomodulatory Properties ◽  
Acetyl Cysteine ◽  
High Doses ◽  
The Brain

Glutathione (GSH) has poor pharmacokinetic properties; thus, several derivatives and biosynthetic precursors have been proposed as GSH-boosting drugs. I-152 is a conjugate of N-acetyl-cysteine (NAC) and S-acetyl-β-mercaptoethylamine (SMEA) designed to release the parent drugs (i.e., NAC and β-mercaptoethylamine or cysteamine, MEA). NAC is a precursor of L-cysteine, while MEA is an aminothiol able to increase GSH content; thus, I-152 represents the very first attempt to combine two pro-GSH molecules. In this review, the in-vitro and in-vivo metabolism, pro-GSH activity and antiviral and immunomodulatory properties of I-152 are discussed. Under physiological GSH conditions, low I-152 doses increase cellular GSH content; by contrast, high doses cause GSH depletion but yield a high content of NAC, MEA and I-152, which can be used to resynthesize GSH. Preliminary in-vivo studies suggest that the molecule reaches mouse organs, including the brain, where its metabolites, NAC and MEA, are detected. In cell cultures, I-152 replenishes experimentally depleted GSH levels. Moreover, administration of I-152 to C57BL/6 mice infected with the retroviral complex LP-BM5 is effective in contrasting virus-induced GSH depletion, exerting at the same time antiviral and immunomodulatory functions. I-152 acts as a pro-GSH agent; however, GSH derivatives and NAC cannot completely replicate its effects. The co-delivery of different thiol species may lead to unpredictable outcomes, which warrant further investigation.

Seizures in Rats Associated with Divalent Cation Inhibition of Na+–K+-ATP'ase

1971 ◽  
Vol 49 (11) ◽  
pp. 1217-1224 ◽  
Author(s):  
J. Donaldson ◽  
T. St-Pierre ◽  
J. Minnich ◽  
A. Barbeau
Keyword(s):  
Divalent Cation ◽  
Regional Analysis ◽  
Intraventricular Injection ◽  
Specific Inhibition ◽  
Low Doses ◽  
High Doses ◽  
Very High

In vitro determination of rat brain microsomal ATP'ase activity revealed specific inhibition of the Na+–K+-ATP'ase by cations in the order Zn2+ > Cu2+ > Fe2+ > Mn2+. Intraventricular injection of the same cations or of ouabain resulted in convulsions. Regional analysis of ATP'ase from brains of rats after convulsions showed inhibited Na+–K+-ATP'ase activity in hippocampus and hypothalamus. Hippocampus and hypothalamus were found to have the highest Na+–K+-ATP'ase activity in the rat brain.The potent inhibitors of Na+–K+-ATP'ase in vitro (ouabain, Zn2+, and Cu2+) were similarly effective in vivo (hippocampus and hypothalamus), while the inhibitors relatively ineffective in vitro (Fe2+ and Mn2+) were similarly of low potency in vivo. The potent inhibitors of Na+–K+-ATP'ase caused convulsions at low doses; the ineffective inhibitors caused convulsions only at very high doses.

scholarly journals Phasic oxygen dynamics confounds fast choline-sensitive biosensor signals in the brain of behaving rodents

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ricardo M Santos ◽  
Anton Sirota
Keyword(s):  
Field Potential ◽  
Choline Oxidase ◽  
Fast Time ◽  
In Vivo Experiments ◽  
Highly Sensitive ◽  
Cortical Physiology ◽  
Oxygen Dynamics ◽  
The Brain

Cholinergic fast time-scale modulation of cortical physiology is critical for cognition, but direct local measurement of neuromodulators in vivo is challenging. Choline oxidase (ChOx)-based electrochemical biosensors have been used to capture fast cholinergic signals in behaving animals. However, these transients might be biased by local field potential and O2-evoked enzymatic responses. Using a novel Tetrode-based Amperometric ChOx (TACO) sensor, we performed highly sensitive and selective simultaneous measurement of ChOx activity (COA) and O2. In vitro and in vivo experiments, supported by mathematical modeling, revealed that non-steady-state enzyme responses to O2 give rise to phasic COA dynamics. This mechanism accounts for most of COA transients in the hippocampus, including those following locomotion bouts and sharp-wave/ripples. Our results suggest that it is unfeasible to probe phasic cholinergic signals under most behavioral paradigms with current ChOx biosensors. This confound is generalizable to any oxidase-based biosensor, entailing rigorous controls and new biosensor designs.

Preclinical Drug Discovery in Colorectal Cancer: A Focus on Natural Compounds

2021 ◽  
Vol 22 ◽  
Author(s):  
Heshu Sulaiman Rahman
Keyword(s):  
Colorectal Cancer ◽  
Malignant Cell ◽  
Natural Compounds ◽  
In Vivo Experiments ◽  
M Phase ◽  
Cell Propagation ◽  
New Feature ◽  
High Doses

Background: Colorectal cancer (CRC) is considered one of the most predominant and deadly cancer globally. Nowadays, the main clinical management for this cancer includes chemotherapy and surgery, however, these treatments result in the occurrence of drug resistance and severe side effects, and thus it is a crucial requirement to discover an alternative and potential therapy for CRC treatment. Numerous cancers therapeutic were initially recognized from natural metabolites utilized in traditional medicine and several recent types of research have shown that many natural products own potential effects against CRC and may assist the action of chemotherapy for treatment of CRC. It has been indicated that most patients are well tolerated by natural compounds without showing any toxicity signs even at high doses. Conventional chemotherapeutics interaction with medicinal natural compounds presents a new feature in cancer exploration and treatment. Most of the natural compounds overwhelm malignant cell propagation by apoptosis initiation of CRC cells and arresting of the cell cycle (especially at G, S, and G2/M phase) that result in inhibition of tumor growth. Objective: This mini-review aimed to focus on natural compounds (alkaloids, flavonoids, polysaccharides, polyphenols, terpenoids, lactones, quinones, etc.) that were identified to have anti-CRC activity in vitro on CRC cell lines and/or in vivo experiments on animal models. Conclusion: Most of the studied active natural compounds possess anti-CRC activity via different mechanisms and pathways in vitro and in vivo that might be used as assistance by clinicians to support chemotherapy therapeutic strategy and treatment doses for cancer patients.

THE EFFECT OF EXOGENOUS RIBONUCLEIC ACID ON ALKALINE PHOSPHATASE ACTIVITY IN THE OVARIECTOMIZED MOUSE UTERUS

1968 ◽  
Vol 57 (3) ◽  
pp. 465-472 ◽  
Author(s):  
A. Maher Mansour
Keyword(s):  
Alkaline Phosphatase ◽  
Alkaline Phosphatase Activity ◽  
Ribonucleic Acid ◽  
Mouse Uterus ◽  
Ovariectomized Mice ◽  
Before And After ◽  
High Doses ◽  
Very High

ABSTRACT RNA from tissues subjected to very high doses of 17β-oestradiol in vivo and in vitro was injected into the uteri of ovariectomized mice before and after ether washing of the RNA. Alkaline phosphatase content of the atrophied uterus was measured after the RNA injections. Results indicate that alkaline phosphatase induction is due to RNA and that ether washing completely eliminates hormonal contamination. The role played by the hormone-cytoplasm requires further attention.

Characterization of soluble CD39 (SolCD39/NTPDase1) from PiggyBac nonviral system as a tool to control the nucleotides level

2019 ◽  
Vol 476 (11) ◽  
pp. 1637-1651
Author(s):  
Liziane Raquel Beckenkamp ◽  
Isabele Cristiana Iser ◽  
Giovana Ravizzoni Onzi ◽  
Dieine Maira Soares da Fontoura ◽  
Ana Paula Santin Bertoni ◽  
...  
Keyword(s):  
Purinergic Signaling ◽  
Hydrolytic Activity ◽  
Soluble Form ◽  
Purinergic System ◽  
In Vivo Experiments ◽  
High Doses ◽  
And Migration

Abstract Extracellular ATP (eATP) and its metabolites have emerged as key modulators of different diseases and comprise a complex pathway called purinergic signaling. An increased number of tools have been developed to study the role of nucleotides and nucleosides in cell proliferation and migration, influence on the immune system and tumor progression. These tools include receptor agonists/antagonists, engineered ectonucleotidases, interference RNAs and ectonucleotidase inhibitors that allow the control and quantification of nucleotide levels. NTPDase1 (also called apyrase, ecto-ATPase and CD39) is one of the main enzymes responsible for the hydrolysis of eATP, and purified enzymes, such as apyrase purified from potato, or engineered as soluble CD39 (SolCD39), have been widely used in in vitro and in vivo experiments. However, the commercial apyrase had its effects recently questioned and SolCD39 exhibits limitations, such as short half-life and need of high doses to reach the expected enzymatic activity. Therefore, this study investigated a non-viral method to improve the overexpression of SolCD39 and evaluated its impact on other enzymes of the purinergic system. Our data demonstrated that PiggyBac transposon system proved to be a fast and efficient method to generate cells stably expressing SolCD39, producing high amounts of the enzyme from a limited number of cells and with high hydrolytic activity. In addition, the soluble form of NTPDase1/CD39 did not alter the expression or catalytic activity of other enzymes from the purinergic system. Altogether, these findings set the groundwork for prospective studies on the function and therapeutic role of eATP and its metabolites in physiological and pathological conditions.

scholarly journals Multifunctional Superparamagnetic Stiff Nanoreservoirs for Blood Brain Barrier Applications

Nanomaterials ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 449 ◽  
Author(s):  
Zulema Vargas-Osorio ◽  
Andrés Da Silva-Candal ◽  
Yolanda Piñeiro ◽  
Ramón Iglesias-Rey ◽  
Tomas Sobrino ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Neurological Diseases ◽  
Developed Countries ◽  
Large Set ◽  
In Vivo Experiments ◽  
Liver And Kidney ◽  
The Brain

Neurological diseases (Alzheimer’s disease, Parkinson’s disease, and stroke) are becoming a major concern for health systems in developed countries due to the increment of ageing in the population, and many resources are devoted to the development of new therapies and contrast agents for selective imaging. However, the strong isolation of the brain by the brain blood barrier (BBB) prevents not only the crossing of pathogens, but also a large set of beneficial drugs. Therefore, an alternative strategy is arising based on the anchoring to vascular endothelial cells of nanoplatforms working as delivery reservoirs. In this work, novel injectable mesoporous nanorods, wrapped by a fluorescent magnetic nanoparticles envelope, are proposed as biocompatible reservoirs with an extremely high loading capacity, surface versatility, and optimal morphology for enhanced grafting to vessels during their diffusive flow. Wet chemistry techniques allow for the development of mesoporous silica nanostructures with tailored properties, such as a fluorescent response suitable for optical studies, superparamagnetic behavior for magnetic resonance imaging MRI contrast, and large range ordered porosity for controlled delivery. In this work, fluorescent magnetic mesoporous nanorods were physicochemical characterized and tested in preliminary biological in vitro and in vivo experiments, showing a transversal relaxivitiy of 324.68 mM−1 s−1, intense fluorescence, large specific surface area (300 m2 g−1), and biocompatibility for endothelial cells’ uptake up to 100 µg (in a 80% confluent 1.9 cm2 culture well), with no liver and kidney disability. These magnetic fluorescent nanostructures allow for multimodal MRI/optical imaging, the allocation of therapeutic moieties, and targeting of tissues with specific damage.

scholarly journals Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain

2021 ◽  
Vol 11 (12) ◽  
pp. 1561
Author(s):  
Igor Manzhulo ◽  
Olga Manzhulo ◽  
Anna Tyrtyshnaia ◽  
Arina Ponomarenko ◽  
Sophia Konovalova ◽  
...  
Keyword(s):  
Chronic Constriction Injury ◽  
Hippocampal Neurogenesis ◽  
Liquid Chromatography Mass Spectrometry ◽  
Cold Allodynia ◽  
In Vivo Experiments ◽  
Mass Spectrometry Technique ◽  
Spectrometry Technique ◽  
The Brain

The present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury (CCI) model. We analyzed the dynamics of GFAP-positive astroglia and S100β-positive astroglia activity, the expression of nerve growth factor (NGF), and two subunits of the NMDA receptor (NMDAR1 and NMDAR2A) in the hippocampi of the experimental animals. Hippocampal neurogenesis was evaluated by immunohistochemical detection of DCX. Analysis of N-acylethanolamines in plasma and in the brain was performed using the liquid chromatography-mass spectrometry technique. In vitro and in vivo experiments show that synaptamide (1) reduces cold allodynia, (2) improves working memory and locomotor activity, (3) stabilizes neurogenesis and astroglial activity, (4) enhances the expression of NGF and NMDAR1, (5) increases the concentration of Ca2+ in astrocytes, and (6) increases the production of N-acylethanolamines. The results of the present study demonstrate that synaptamide affects the activity of hippocampal astroglia, resulting in faster recovery after CCI.

5β-Reductase activity in the brain and cloacal gland of male and female embryos in the Japanese quail (Coturnix coturnix japonica)

1984 ◽  
Vol 102 (1) ◽  
pp. 77-81 ◽  
Author(s):  
J. Balthazart ◽  
M. A. Ottinger
Keyword(s):  
Reductase Activity ◽  
Young Male ◽  
Testosterone Metabolism ◽  
Male And Female ◽  
Coturnix Coturnix ◽  
Female Quail ◽  
In Vitro Technique ◽  
The Brain ◽  
Cloacal Gland

ABSTRACT Testosterone metabolism was studied by an in-vitro technique in the brain and cloacal gland of young male and female quail at different ages ranging from 7 days of incubation to 2 days after hatching. Very active metabolism, leading almost exclusively to the production of 5β-reduced compounds, was observed. 5β-Reductase activity remained high throughout the incubation period in the hypothalamus, decreased around the time of hatching in the cerebellum and decreased progressively between days 7 and 15 of incubation in the cloacal gland. These changes could be involved in the control of sexual differentiation: the high 5β-reductase in the brain possibly protects males from being behaviourally demasculinized by their endogenous testosterone while the decreasing 5β-reductase in the cloacal gland would progressively permit the masculinization of that structure. J. Endocr. (1984) 102, 77–81

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